Eligibility for Magnetic Resonance Imaging Screening in the United Kingdom: Effect of Strict Selection Criteria and Anonymous DNA Testing on Breast Cancer Incidence in the MARIBS Study
- D. Gareth R. Evans1,
- Fiona Lennard2,
- Linda J. Pointon4,
- Susan J. Ramus3,
- Simon A. Gayther3,
- Nayanta Sodha2,
- Gek E. Kwan-Lim4,
- Martin O. Leach4,
- Ruth Warren6,
- Deborah Thompson5,
- Douglas F. Easton5,
- Rosalind Eeles2 and
- on behalf of The UK study of MRI screening for breast cancer in women at high risk (MARIBS)
- 1Genetic Medicine, University of Manchester, Manchester Academic Health Science Center, Central Manchester University Hospitals NHS Foundation Trust, St. Mary's Hospital, Manchester, United Kingdom; 2Cancer Genetics Unit, Royal Marsden NHS Foundation Trust and 3Gynaecological Cancer Research Laboratory, UCL EGA Institute for Women's Health, University College London, London, United Kingdom; 4Cancer Research UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 5Cancer Research UK Genetic Epidemiology Department, Strangeways Research and 6Department of Radiology, Addenbrookes Hospital, Cambridge, United Kingdom
- Requests for reprints:
D. Gareth R. Evans, Consultant Clinical Geneticist, University Department of Medical Genetics and Regional Genetic Service, Central Manchester Foundation Trust, St. Mary's Hospital, Hathersage Road, Manchester, M13 0JH, United Kingdom. Phone: 44-0-161-276-6206; Fax: 44-0-161-276-6145. E-mail: Gareth.evans{at}cmft.nhs.uk
Abstract
Introduction: A UK multicenter study compared the performance of contrast enhanced-magnetic resonance imaging with X-Ray Mammography in women at high-risk of breast cancer commencing in 1997. Selection criteria were used to identify women with at least 0.9% annual risk of breast cancer.
Methods: Women at high breast cancer risk, with a strong family history and/or high probability of a BRCA1/BRCA2/TP53 mutation, were recruited from 22 centers. Those not known as gene carriers were asked to give a blood sample, which was tested anonymously for mutations. Women ages 35 to 49 years were offered annual screening for 2 to 7 years. Study eligibility at entry was assessed retrospectively by detailed examination of pedigrees and overall eligibility accounting for computer risk assessment and mutation results.
Results: Seventy-eight of 837 (9%) women entered for screening were ineligible using the strict entry criteria. Thirty-nine cancers were detected in 1,869 women-years in study (incidence 21 per 1,000). Including 3,561 further years follow-up, 28 more breast cancers were identified (12 of 1,000). Incidence rates for 759 eligible women were 22 of 1,000 in study and 13 of 1,000 in total follow-up, compared with 9 of 1,000 and 4 of 1,000, respectively, in 78 ineligible women. Breast cancer rates were higher for BRCA2 than BRCA1 after testing anonymized samples in this selected population at 65 of 1,000 in study and 36 of 1,000 in total follow-up for BRCA2 compared with 44 of 1,000 and 27 of 1,000 for BRCA1.
Conclusions: Strict enforcement of study criteria would have minimally improved the power of the study, whereas testing for BRCA1/2 in advance would have substantially increased the detection rates. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2123–31)
Footnotes
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Grant support: The national study was supported by a grant from the Medical Research Council (G9600413) and Cancer Research UK Project Grant G5047/A5830. The cost of the magnetic resonance imaging studies was paid for from subvention funding for research from the United Kingdom National Health Service. The protocol is based in part on developments supported by the Cancer Research UK and the Yorkshire Cancer Research Campaign. Contributions toward training and education have been made by Schering Healthcare Ltd. and Oracle Education. D.F. Easton and D. Thompson are funded by Cancer Research UK. R. Eeles is funded by The Institute of Cancer Research and Higher Education Funding Council for England. S.J. Ramus is funded by the Mermaid component of the Eve Appeal. This work was carried out at three centers who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme namely: Central Manchester Foundation Trust, the Royal Marsden Foundation Trust, and University College Hospital London.
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Note: See Appendix for full authorship list.
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- Accepted May 5, 2009.
- Received February 13, 2009.
- Revision received May 4, 2009.
